Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZQT61Q)

• DOT Name: Scm-like with four MBT domains protein 2 (SFMBT2)
• Synonyms: Scm-like with 4 MBT domains protein 2
• Gene Name: SFMBT2
• Related Disease:
  HER2/NEU overexpressing breast cancer
  Beta thalassemia
  Estrogen-receptor positive breast cancer
  Gastric cancer
  Stomach cancer
  Osteoarthritis
  Carcinoma of liver and intrahepatic biliary tract
  Hepatitis B virus infection
  Liver cancer
  Metastatic prostate carcinoma
  Prostate cancer
  Prostate carcinoma
  Esophageal squamous cell carcinoma
• UniProt ID: SMBT2_HUMAN
• PDB ID: 1WJR
• Pfam ID: PF02820 ; PF00536 ; PF12140
• Sequence:
  MESTLSASNMQDPSSSPLEKCLGSANGNGDLDSEEGSSLEETGFNWGEYLEETGASAAPH
  TSFKHVEISIQSNFQPGMKLEVANKNNPDTYWVATIITTCGQLLLLRYCGYGEDRRADFW
  CDVVIADLHPVGWCTQNNKVLMPPDAIKEKYTDWTEFLIRDLTGSRTAPANLLEGPLRGK
  GPIDLITVGSLIELQDSQNPFQYWIVSVIENVGGRLRLRYVGLEDTESYDQWLFYLDYRL
  RPVGWCQENKYRMDPPSEIYPLKMASEWKCTLEKSLIDAAKFPLPMEVFKDHADLRSHFF
  TVGMKLETVNMCEPFYISPASVTKVFNNHFFQVTIDDLRPEPSKLSMLCHADSLGILPVQ
  WCLKNGVSLTPPKGYSGQDFDWADYHKQHGAQEAPPFCFRNTSFSRGFTKNMKLEAVNPR
  NPGELCVASVVSVKGRLMWLHLEGLQTPVPEVIVDVESMDIFPVGWCEANSYPLTAPHKT
  VSQKKRKIAVVQPEKQLPPTVPVKKIPHDLCLFPHLDTTGTVNGKYCCPQLFINHRCFSG
  PYLNKGRIAELPQSVGPGKCVLVLKEVLSMIINAAYKPGRVLRELQLVEDPHWNFQEETL
  KAKYRGKTYRAVVKIVRTSDQVANFCRRVCAKLECCPNLFSPVLISENCPENCSIHTKTK
  YTYYYGKRKKISKPPIGESNPDSGHPKPARRRKRRKSIFVQKKRRSSAVDFTAGSGEESE
  EEDADAMDDDTASEETGSELRDDQTDTSSAEVPSARPRRAVTLRSGSEPVRRPPPERTRR
  GRGAPAASSAEEGEKCPPTKPEGTEDTKQEEEERLVLESNPLEWTVTDVVRFIKLTDCAP
  LAKIFQEQDIDGQALLLLTLPTVQECMELKLGPAIKLCHQIERVKVAFYAQYAN
• Function: Transcriptional repressor of HOXB13 gene.
• KEGG Pathway: Polycomb repressive complex (hsa03083)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
HER2/NEU overexpressing breast cancer	DISYKID5	Definitive	Altered Expression	[1]
Beta thalassemia	DIS5RCQK	Strong	Biomarker	[2]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Genetic Variation	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[2]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Disputed	Altered Expression	[5]
Hepatitis B virus infection	DISLQ2XY	Disputed	Altered Expression	[5]
Liver cancer	DISDE4BI	Disputed	Altered Expression	[5]
Metastatic prostate carcinoma	DISVBEZ9	Disputed	Altered Expression	[6]
Prostate cancer	DISF190Y	Disputed	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Disputed	Altered Expression	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Biomarker	[7]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[13]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[18]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Scm-like with four MBT domains protein 2 (SFMBT2).	[19]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Scm-like with four MBT domains protein 2 (SFMBT2).	[15]

References

• [1] Biological function of long noncoding RNA snaR in HER2-positive breast cancer cells.Tumour Biol. 2017 Jun;39(6):1010428317707374. doi: 10.1177/1010428317707374.
• [2] Circ-SFMBT2 promotes the proliferation of gastric cancer cells through sponging miR-182-5p to enhance CREB1 expression.Cancer Manag Res. 2018 Nov 16;10:5725-5734. doi: 10.2147/CMAR.S172592. eCollection 2018.
• [3] Genome-wide association study of germline variants and breast cancer-specific mortality.Br J Cancer. 2019 Mar;120(6):647-657. doi: 10.1038/s41416-019-0393-x. Epub 2019 Feb 21.
• [4] Down-regulated in OA cartilage, SFMBT2 contributes to NF-B-mediated ECM degradation.J Cell Mol Med. 2018 Nov;22(11):5753-5758. doi: 10.1111/jcmm.13826. Epub 2018 Aug 22.
• [5] Analysis of long non-coding RNA (lncRNA) expression in hepatitis B patients.Bosn J Basic Med Sci. 2018 May 20;18(2):150-161. doi: 10.17305/bjbms.2018.2800.
• [6] SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells.Oncotarget. 2016 Jul 26;7(30):48250-48264. doi: 10.18632/oncotarget.10198.
• [7] The biogenesis and biological functions of circular RNAs and their molecular diagnostic values in cancers.J Clin Lab Anal. 2020 Jan;34(1):e23049. doi: 10.1002/jcla.23049. Epub 2019 Sep 25.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.